This is a request for five years of salary support via a NIH Independent Scientist Award (K02). I have long sought to integrate psychosocial and biological models of depression, and I hope to use the RCA to enhance my understanding of basic neurobiology and developmental issues relevant to its nature and treatment. I also want to enhance the relevance of my work to applied clinical settings (effectiveness). In particular, I am interested in whether cognitive therapy has a more enduring effect than drugs in the treatment of depression. Earlier studies suggested that this might be the case, but the recent NIH TDCRP found cognitive therapy to be less effective than drugs in the treatment of more severely depressed outpatients and reported little evidence of any enduring effect. Both sets of studies have been criticized for failing to provide optimal implementations of the respective modalities, drugs in the earlier studies and cognitive therapy in the TDCRP. We are currently conducting (with colleagues at Penn) a placebo-controlled comparison of cognitive therapy versus drugs in the treatment of more severely depressed outpatients that seek to address both sets of concerns. I am also collaborating with Neil Jacobson in Seattle in a similar placebo-controlled trial designed to determine whether behavioral activation (which is simpler to implement) carries the full weight of change in cognitive therapy. Further, we plan to examine (with colleagues at Penn and Rush) whether adding cognitive therapy to drugs can both enhance the breadth of response and obviate the need to keep patients on long-term maintenance medications. Finally, we are collaborating with colleagues at each of these sites to study the impact of treatment on the offspring of our depressed patients. We think that more can be done to study the full range of benefits associated with successful treatment. My goal has been to examine the role of both psychological and biological processes in the moderation and medication of treatment effects and to do so in a manner that has the greatest possible impact on actual clinical practice. I hope to use my growing expertise in neurobiology and development to better understand the processes that underlie the treatment and prevention of depression and to use that understanding to enhance the effectiveness of clinical practice in applied settings.